3R8I
Crystal Structure of PPARgamma with an achiral ureidofibrate derivative (RT86)
Summary for 3R8I
| Entry DOI | 10.2210/pdb3r8i/pdb |
| Related | 2I4J 2I4P 2I4Z |
| Descriptor | Peroxisome proliferator-activated receptor gamma, 2-(4-{2-[1,3-benzoxazol-2-yl(heptyl)amino]ethyl}phenoxy)-2-methylpropanoic acid (3 entities in total) |
| Functional Keywords | protein-dna complex, bundle of alpha-helices, small four-stranded beta-sheet, transcription, activator, diabetes mellitus, obesity, transcription regulation, dna binding, phosphorylation, nucleus |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: P37231 |
| Total number of polymer chains | 2 |
| Total formula weight | 65826.21 |
| Authors | Pochetti, G.,Montanari, R.,Loiodice, F.,Laghezza, A.,Fracchiolla, G.,Lavecchia, A.,Novellino, E.,Crestani, M. (deposition date: 2011-03-24, release date: 2012-01-11, Last modification date: 2023-09-13) |
| Primary citation | Porcelli, L.,Gilardi, F.,Laghezza, A.,Piemontese, L.,Mitro, N.,Azzariti, A.,Altieri, F.,Cervoni, L.,Fracchiolla, G.,Giudici, M.,Guerrini, U.,Lavecchia, A.,Montanari, R.,Di Giovanni, C.,Paradiso, A.,Pochetti, G.,Simone, G.M.,Tortorella, P.,Crestani, M.,Loiodice, F. Synthesis, characterization and biological evaluation of ureidofibrate-like derivatives endowed with peroxisome proliferator-activated receptor activity. J.Med.Chem., 55:37-54, 2012 Cited by PubMed Abstract: A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARγ-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARγ target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARα target genes indicating that their in vivo effects stemmed from an activation of both PPARα and γ. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated. PubMed: 22081932DOI: 10.1021/jm201306q PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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